Abstract
Nuclei segmentation has great significance in biomedical applications as the preliminary step for disease diagnosis and treatment analysis. In this study, we propose a model for automated nuclei identification of varying cell shapes and types from microscopy images. Identifying nuclei helps to understand the underlying mechanism of various diseases in their early stages and provides solutions to enable faster cures. The foremost aim of the study is to develop a lightweight model, capable of segmenting varied shapes and sizes. The proposed architecture exploits multi-scale low-level features following dense high-level feature extraction with multi-feature fusion and special skip connections resulting in enhanced learning capability. The multi-scale feature extractor module extracts low-level information which is further processed using attention-based dense connections to extract semantically meaningful information. The special short-skip residual connections replacing long-skip connections reduced the semantic gap between encoder–decoder features. Moreover, the context encoder module extracts higher-level contextual information of different receptive fields using dilated convolutions making the model robust to different shapes and sizes. The higher-level feature maps propagate upward the decoder connections following the shared attention mechanism of an encoder to decoder features to reconstruct a better segmentation map. Moreover, the evaluation scheme following the proposed test-time augmentation operations improved the mean segmentation performance. The experiments on KDSB18, Synthetic cells, Triple-negative breast cancer (TNBC), MoNuSeg, CryoNuSeg, and BUS datasets demonstrate the suitability of the model for the nuclei segmentation tasks. The DRI-UNet model holds good segmentation performance outperforming baseline architecture by 8.12%, 4.71%, 10.19%, 2.46%, 3.14%, 8.91%, and 9.32% on KDSB18, synthetic cells, TNBC, MoNuSeg, CryoNuSeg, CVC-ClinicDB, and BUS datasets, respectively. We further conducted generalization tests of the proposed model for cross-dataset validation, and two independent MIS datasets confirm model effectiveness for nuclei cell and biomedical image segmentation.
Similar content being viewed by others
Data availability
The data and source code associated with the manuscript will be made available after the reasonable request.
Notes
References
Anwar SM, Majid M, Qayyum A, Awais M, Alnowami M, Khan MK (2018) Medical image analysis using convolutional neural networks: a review. J Med Syst 42(11):1–13
Mohapatra S, Patra D, Satpathy S (2014) An ensemble classifier system for early diagnosis of acute lymphoblastic leukemia in blood microscopic images. Neural Comput Appl 24(7):1887–1904
Morid MA, Borjali A, Del Fiol G (2021) A scoping review of transfer learning research on medical image analysis using imagenet. Comput Biol Med 128:104115
Al-Masni MA, Kim DH (2021) CMM-Net: contextual multi-scale multi-level network for efficient biomedical image segmentation. Sci Rep 11(1):1–18
Caicedo JC, Goodman A, Karhohs KW, Cimini BA, Ackerman J, Haghighi M, Heng C, Becker T, Doan M, McQuin C, Rohban M (2019) Nucleus segmentation across imaging experiments: the 2018 data science bowl. Nat Methods 16(12):1247–1253
Long F (2020) Microscopy cell nuclei segmentation with enhanced U-Net. BMC Bioinform 21(1):1–12
Kaggle (2018) Kaggle data science bowl challenge—KDSB. Retrieved Jan 10, 2022, from https://www.kaggle.com/c/data-science-bowl-2018
Krishnadas P, Chadaga K, Sampathila N, Rao S, Prabhu S (2022) Classification of malaria using object detection models. Informatics 9(4):76
Punn N S, & Agarwal S (2020) Inception u-net architecture for semantic segmentation to identify nuclei in microscopy cell images. ACM Trans Multimed Comput Commun Appl (TOMM) 16(1): 1–15
Zhang Z, Wu C, Coleman S, Kerr D (2020) DENSE-INception U-net for medical image segmentation. Comput Methods Progr Biomed 192:105395
Szegedy C, Liu W, Jia Y, Sermanet P, Reed S, Anguelov D, & Rabinovich A (2015) Going deeper with convolutions. In: proceedings of the IEEE conference on computer vision and pattern recognition (pp 1–9)
Huang G, Liu Z, Van Der Maaten L, & Weinberger K Q (2017) Densely connected convolutional networks. In: proceedings of the IEEE conference on computer vision and pattern recognition (pp 4700–4708)
He K, Zhang X, Ren S, & Sun J (2016) Deep residual learning for image recognition. In: proceedings of the IEEE conference on computer vision and pattern recognition (pp 770–778)
Sharma A, Mishra PK (2022) Covid-MANet: multi-task attention network for explainable diagnosis and severity assessment of COVID-19 from CXR images. Pattern Recognit 1(131):108826
Ibtehaz N, Rahman MS (2020) MultiResUNet: rethinking the U-Net architecture for multimodal biomedical image segmentation. Neural Netw 121:74–87
Long J, Shelhamer E, & Darrell T (2015). Fully convolutional networks for semantic segmentation. In: proceedings of the IEEE conference on computer vision and pattern recognition (pp 3431–3440)
Badrinarayanan V, Kendall A, Cipolla R (2017) Segnet: a deep convolutional encoder-decoder architecture for image segmentation. IEEE Trans Pattern Anal Mach Intell 39(12):2481–2495
Ronneberger O, Fischer P, & Brox T (2015) U-net: convolutional networks for biomedical image segmentation. In: international conference on medical image computing and computer-assisted intervention (pp 234–241). Springer, Cham
Oktay O, Schlemper J, Folgoc L L, Lee M, Heinrich M, Misawa K, & Rueckert D (2018) Attention u-net: Learning where to look for the pancreas. arXiv preprint arXiv:1804.03999
Zhou Z, Siddiquee MMR, Tajbakhsh N, Liang J (2019) Unet++: Redesigning skip connections to exploit multiscale features in image segmentation. IEEE Trans Med Imaging 39(6):1856–1867
Alom MZ, Yakopcic C, Hasan M, Taha TM, Asari VK (2019) Recurrent residual U-Net for medical image segmentation. J Med Imaging 6(1):014006
Zhang Z, Liu Q, Wang Y (2018) Road extraction by deep residual u-net. IEEE Geosci Remote Sens Lett 15(5):749–753
Lou A, Guan S, Loew M (2021) DC-UNet: rethinking the U-Net architecture with dual channel efficient CNN for medical image segmentation. In: medical imaging 2021: image processing 11596:758–768 SPIE
Srivastava A, Jha D, Chanda S, Pal U, Johansen HD, Johansen D, Riegler MA, Ali S, Halvorsen P (2021) Msrf-net: a multi-scale residual fusion network for biomedical image segmentation. IEEE J Biomed Health Inform 26(5):2252–2263
Tomar N K, Jha D, Riegler M A, Johansen H D, Johansen D, Rittscher J & Ali S (2022) Fanet: a feedback attention network for improved biomedical image segmentation. IEEE Trans Neural Net Learn Syst
Lou A, Guan S, Loew M (2023) Cfpnet-m: a light-weight encoder-decoder based network for multimodal biomedical image real-time segmentation. Comput Biol Med 154:106579
Suman S, Tiwari AK, Singh K (2023) Computer-aided diagnostic system for hypertensive retinopathy: a review. Comput Methods Programs Biomed 240:107627
Chen LC, Papandreou G, Kokkinos I, Murphy K, Yuille AL (2017) Deeplab: semantic image segmentation with deep convolutional nets, atrous convolution, and fully connected crfs. IEEE Trans Pattern Anal Mach Intell 40(4):834–848
He K, Zhang X, Ren S, Sun J (2015) Spatial pyramid pooling in deep convolutional networks for visual recognition. IEEE Trans Pattern Anal Mach Intell 37(9):1904–1916
Zhao H, Shi J, Qi X, Wang X, & Jia J (2017) Pyramid scene parsing network. In: proceedings of the IEEE conference on computer vision and pattern recognition (pp 2881–2890)
Milletari F, Navab N, & Ahmadi S A (2016) V-net: fully convolutional neural networks for volumetric medical image segmentation. In: 2016 fourth international conference on 3D vision (3DV) (pp 565–571). IEEE
Diakogiannis FI, Waldner F, Caccetta P, Wu C (2020) ResUNet-a: a deep learning framework for semantic segmentation of remotely sensed data. ISPRS J Photogramm Remote Sens 162:94–114
Jha D, Smedsrud P H, Riegler M A, Johansen D, De Lange T, Halvorsen P & Johansen H D (2019) Resunet++: an advanced architecture for medical image segmentation. In: 2019 IEEE international symposium on multimedia (ISM) (pp 225–2255). IEEE
Zeng Z, Xie W, Zhang Y, Lu Y (2019) RIC-Unet: an improved neural network based on Unet for nuclei segmentation in histology images. Ieee Access 7:21420–21428
Zhang J, Jin Y, Xu J, Xu X, & Zhang Y (2018). Mdu-net: multi-scale densely connected u-net for biomedical image segmentation. arXiv preprint arXiv:1812.00352
Jha D, Riegler M A, Johansen D, Halvorsen P, & Johansen H D (2020) Doubleu-net: a deep convolutional neural network for medical image segmentation. In: 2020 IEEE 33rd international symposium on computer-based medical systems (CBMS) (pp 558–564). IEEE
Gu Z, Cheng J, Fu H, Zhou K, Hao H, Zhao Y, Zhang T, Gao S, Liu J (2019) Ce-net: context encoder network for 2d medical image segmentation. IEEE Trans Med Imaging 38(10):2281–2292
Dolz J, Gopinath K, Yuan J, Lombaert H, Desrosiers C, Ayed IB (2018) HyperDense-Net: a hyper-densely connected CNN for multi-modal image segmentation. IEEE Trans Med Imaging 38(5):1116–1126
Punn NS, Agarwal S (2022) RCA-IUnet: a residual cross-spatial attention-guided inception U-Net model for tumor segmentation in breast ultrasound imaging. Mach Vis Appl 33(2):1–10
Yu F, Wang D, Shelhamer E, & Darrell T (2018) Deep layer aggregation. In: Proceedings of the IEEE conference on computer vision and pattern recognition (pp 2403–2412)
Yadavendra, Chand S (2022) Semantic segmentation of human cell nucleus using deep U-Net and other versions of U-Net models. Net Comput Neural Syst 1–20
Azad R, Asadi-Aghbolaghi M, Fathy M, & Escalera S (2019) Bi-directional ConvLSTM U-Net with densley connected convolutions. In: proceedings of the IEEE/CVF international conference on computer vision workshops (pp 0-0)
Gudhe NR, Behravan H, Sudah M, Okuma H, Vanninen R, Kosma VM, Mannermaa A (2021) Multi-level dilated residual network for biomedical image segmentation. Sci Rep 11(1):14105
Ashraf H, Waris A, Ghafoor MF, Gilani SO, Niazi IK (2022) Melanoma segmentation using deep learning with test-time augmentations and conditional random fields. Sci Rep 12(1):1–16
Moshkov N, Mathe B, Kertesz-Farkas A, Hollandi R, Horvath P (2020) Test-time augmentation for deep learning-based cell segmentation on microscopy images. Sci Rep 10(1):1–7
Senapati MR, Panda G, Dash PK (2014) Hybrid approach using KPSO and RLS for RBFNN design for breast cancer detection. Neural Comput Appl 24(3):745–753
Chadaga K, Prabhu S, Bhat KV, Umakanth S, Sampathila N (2022) Medical diagnosis of COVID-19 using blood tests and machine learning. J Phys Conf Ser 2161(1):012017
Sharma A, Mishra PK (2022) Image enhancement techniques on deep learning approaches for automated diagnosis of COVID-19 features using CXR images. Multimed Tools Appl 81(29):1–42
Lehmussola A, Ruusuvuori P, Selinummi J, Huttunen H, Yli-Harja O (2007) Computational framework for simulating fluorescence microscope images with cell populations. IEEE Trans Med Imaging 26(7):1010–1016
Kaur A, Kaur L, Singh A (2021) GA-UNet: UNet-based framework for segmentation of 2D and 3D medical images applicable on heterogeneous datasets. Neural Comput Appl 33(21):14991–15025
Hubel DH, Wiesel TN (1962) Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J Physiol 160(1):106
Luo P, Ren J, Peng Z, Zhang R, & Li J (2018) Differentiable learning-to-normalize via switchable normalization. arXiv preprint arXiv:1806.10779
Kolařík M, Burget R, Uher V, Říha K, Dutta MK (2019) Optimized high resolution 3d dense-u-net network for brain and spine segmentation. Appl Sci 9(3):404
Karim M, Rahman A, Jares JB, Decker S, Beyan O (2020) A snapshot neural ensemble method for cancer-type prediction based on copy number variations. Neural Comput Appl 32(19):15281–15299
Naylor P, Laé M, Reyal F, Walter T (2018) Segmentation of nuclei in histopathology images by deep regression of the distance map. IEEE Trans Med Imaging 38(2):448–459
Mahbod A, Schaefer G, Bancher B, Löw C, Dorffner G, Ecker R, Ellinger I (2021) CryoNuSeg: a dataset for nuclei instance segmentation of cryosectioned H&E-stained histological images. Comput Biol Med 132:104349
Kumar N, Verma R, Anand D, Zhou Y, Onder OF, Tsougenis E, Chen H, Heng PA, Li J, Hu Z, Wang Y (2019) A multi-organ nucleus segmentation challenge. IEEE Trans Med Imaging 39(5):1380–1391
Sharma A, Mishra PK (2021) Performance analysis of machine learning based optimized feature selection approaches for breast cancer diagnosis. Int J Inf Tech 1–12
Bernal J, Sánchez FJ, Fernández-Esparrach G, Gil D, Rodríguez C, Vilariño F (2015) WM-DOVA maps for accurate polyp highlighting in colonoscopy: validation vs. saliency maps from physicians. Comput Med Imaging Gr 43:99–111
Acknowledgements
We show our sincere gratitude to the University Grant Commission, Government of India, for supporting with a Senior Research Fellowship. The corresponding author greatly acknowledges the IoE grant of Banaras Hindu University.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This article does not contain any studies with human participants or animals performed by any of the authors.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Sharma, A., Mishra, P.K. DRI-UNet: dense residual-inception UNet for nuclei identification in microscopy cell images. Neural Comput & Applic 35, 19187–19220 (2023). https://doi.org/10.1007/s00521-023-08729-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00521-023-08729-0